Phenotypes Associated with This Genotype

Genotype
MGI:3719098

• Allelic Composition: Neu1^tm1Adz/Neu1^tm1Adz
• Genetic Background: either: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * NMRI)

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:76937 )

• 27% of pups in NMRI background and 10-15% in C57BL/6 background died suddenly around weaning age caused by inanition after 1 to 2 days of anorexia

• death occurred in other animals between the ages of 8 and 12 months

respiratory system

respiratory distress ( J:76937 )

• at the end of their lifespan 8 to 12 month of age

behavior/neurological

tremors ( J:76937 )

• at the end of their lifespan 8 to 12 month of age

abnormal gait ( J:76937 )

• at the end of their lifespan 8 to 12 month of age

myoclonus ( J:76937 )

• a shock-like twitch

homeostasis/metabolism

decreased circulating total protein level ( J:76937 )

• mild hypoproteinemia in 8 months or older animals

edema ( J:76937 )

• in penis, forehead developed at 4 to 6 weeks of age and worsened in mice that survived past the 21 days

eyelid edema ( J:76937 )

• developed at 4 to 6 weeks of age and worsened in mice that survived past the 21 days

extremity edema ( J:76937 )

• developed at 4 to 6 weeks of age and worsened in mice that survived past the 21 days

skin edema ( J:76937 )

• developed at 4 to 6 weeks of age and worsened in mice that survived past the 21 days

abnormal urine homeostasis ( J:76937 )

• prominent oligosacchariduria at 1 to 2 month, indicative of sialidosis

vision/eye

eyelid edema ( J:76937 )

• developed at 4 to 6 weeks of age and worsened in mice that survived past the 21 days

skeleton

kyphosis ( J:76937 )

• of the lumbar spine became prominent by the age of 6 months

lordosis ( J:76937 )

• of the cervical and thoracic spine and thoracic spine became prominent by the age of 6 months

muscle

myoclonus ( J:76937 )

• a shock-like twitch

nervous system

myoclonus ( J:76937 )

• a shock-like twitch

abnormal microglial cell morphology ( J:76937 )

• vacuolated microglia and perivascular macrophages in brain

abnormal choroid plexus morphology ( J:76937 )

• extensive storage in the epithelial cells of the choroid plexi and in the endothelial cells of the ependymal layer

abnormal neuron morphology ( J:76937 )

• vacuolated neurons sparsely detected throughout the parenchyma

• no significant cerebellar Purkinje cell degeneration

growth/size/body

eyelid edema ( J:76937 )

• developed at 4 to 6 weeks of age and worsened in mice that survived past the 21 days

decreased body weight ( J:76937 )

• about 25% less weight at birth compared to heterozygous or wild-type littermates

• loss of weight at the end of their life span 8 to 12 month of age

enlarged spleen ( J:76937 )

• starting at 6 weeks of age

spleen hyperplasia ( J:76937 )

• a progressive increase on total cell count up to 5 months

renal/urinary system

accumulation of giant lysosomes in kidney/renal tubule cells ( J:76937 )

• the earliest and most affected lysosome vacuolation

• proximal more than distal and collecting tubules were extensively vacuolated already at 1 month of age

• at 3 months, the epithelial cell of the glomeruli and the Bowman capsule were affected

abnormal urine homeostasis ( J:76937 )

• prominent oligosacchariduria at 1 to 2 month, indicative of sialidosis

hydronephrosis ( J:76937 )

• enlarged kidneys with a markedly dilated renal pelvis

distended urinary bladder ( J:76937 )

• severely distended bladder starting at 6 months of age

ischuria ( J:76937 )

• urinary retention starting at 6 months of age

cellular

abnormal lysosome morphology ( J:76937 )

• prominent vacuolation in all lymphocytes, monocytes and eosinophils, but not in neutrophils

• extensive vacuolation of some cells in most of the systemic organs

• overt abnormalities in the gastrointestinal tract were not evident in the adult mutant mice

• mutant pups that had succumbed suddenly at weaning show the epithelial cells of the villi were markedly dilated with large, apical vacuoles

• inconspicuous lysosomal storage was detected in the heart, skeletal muscle and lung with exception of the endothelial cells lining the capillaries

• in eye, cytoplasmic vacuolation restrictive of the epithelial cell of the ciliary body and the conjunctiva

accumulation of giant lysosomes in kidney/renal tubule cells ( J:76937 )

• the earliest and most affected lysosome vacuolation

• proximal more than distal and collecting tubules were extensively vacuolated already at 1 month of age

• at 3 months, the epithelial cell of the glomeruli and the Bowman capsule were affected

hematopoietic system

abnormal Kupffer cell morphology ( J:76937 )

• appeared ballooned

enlarged spleen ( J:76937 )

• starting at 6 weeks of age

spleen hyperplasia ( J:76937 )

• a progressive increase on total cell count up to 5 months

extramedullary hematopoiesis ( J:76937 )

abnormal microglial cell morphology ( J:76937 )

• vacuolated microglia and perivascular macrophages in brain

immune system

abnormal Kupffer cell morphology ( J:76937 )

• appeared ballooned

enlarged spleen ( J:76937 )

• starting at 6 weeks of age

spleen hyperplasia ( J:76937 )

• a progressive increase on total cell count up to 5 months

abnormal microglial cell morphology ( J:76937 )

• vacuolated microglia and perivascular macrophages in brain

liver/biliary system

abnormal Kupffer cell morphology ( J:76937 )

• appeared ballooned

cardiovascular system

abnormal Kupffer cell morphology ( J:76937 )

• appeared ballooned

integument

skin edema ( J:76937 )

• developed at 4 to 6 weeks of age and worsened in mice that survived past the 21 days

hyperkeratosis ( J:76937 )

• hyperkeratosis of the stomach in mice showing premature death at around weaning

craniofacial

eyelid edema ( J:76937 )

• developed at 4 to 6 weeks of age and worsened in mice that survived past the 21 days

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
glycoproteinosis		DOID:3343	OMIM:256550	J:76937